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Non-Celiac Gluten Sensitivity

gluten sensitivity

Gluten Sensitivity is an umbrella term that refers to any and all problematic health responses to gluten in any body system. We first defined gluten sensitivity in our ground breaking text, Recognizing Celiac Disease first published in 2006.  Gluten Sensitivity includes celiac disease, gluten allergy, and non-celiac gluten sensitivity reactions.1 

Under Pathophysiology in Recognizing Celiac Disease, we confidently published the fact, against the opinion of some noted specialists but in accord with others, that “non-celiac gluten sensitivity” exists as a condition distinct from celiac disease and which must be distinguished from celiac disease for proper treatment of both.

Today, although there lacks a general agreement for the term “gluten sensitivity,” the medical community has accepted the reality of non-celiac gluten sensitivity.

As a result, researchers are calling this condition the “new frontier.” As Dr. Lundin has stated, “We are still challenged with finding stricter clinical criteria for the condition, developing a usable clinical approach for gluten challenge in these individuals, and understanding the pathogenesis of the condition.”2

  • Celiac disease is characterized by a specific immune reaction in the small intestinal lining that is both an innate response (inflammatory) and a humoral response (antibody production) to peptides of gluten that leads to malabsorption of nutrients and increased intestinal permeability (leaky gut).3 The humoral antibody response involves the production of immunoglobulin A (IgA) and immunoglobulin G (IgG). Only persons who have inherited this immune response are at risk to develop celiac disease. Celiac disease results in malabsorption and any of a great number of health problems that can develop from the toxic action of gluten peptides entering the body through a leaky gut.
  • Gluten allergies are immunoglobulin E (IgE) mediated immune responses where hives, asthma, and similar reactions develop. Allergy involves the production of specific antibodies to specific antigens, which would be a peptide of gluten. For example, wheat allergy commonly targets gliadin as the antigen. IgE immune responses appear to be inherited.
  • Non-celiac gluten sensitivity can be diagnosed in those patients with gluten intolerance who do not develop antibodies that are typical either of celiac disease or of wheat allergy and who do not suffer from lesions in the duodenal mucosa characteristic of celiac disease.4 Symptoms that occur soon after gluten ingestion rapidly improve after gluten withdrawal and relapse in a few hours or days after gluten challenge.5

Non-celiac gluten sensitivity is an innate immune response producing mild inflammation (Marsh I class) of the small intestine lining to gluten when present in the diet but negative to production of the anti-EMA, and anti-tTG immunoglobulins (humoral response), which are autoantibodies mounted in celiac disease.


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  1. Libonati, Cleo. Recognizing Celiac Disease, p. IX 

  2. Lundin KE. Non-celiac gluten sensitivity – why worry? BMC Med. 2014 May 23;12:86. doi: 10.1186/1741-7015-12-86. 

  3. Brottveit M, Beitnes AC, Tollefsen S, Bratlie JE, Jahnsen FL, Johansen FE, Sollid LM, Lundin KE. Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity. Am J Gastroenterol. 2013 May;108(5):842-50. doi: 10.1038/ajg.2013.91. 

  4. Czaja-Bulsa G. Non coeliac gluten sensitivity – A new disease with gluten intolerance. Clin Nutr. 2014 Aug 29. pii: S0261-5614(14)00218-0. doi: 10.1016/j.clnu.2014.08.012. 

  5. Caio G, Volta U, Tovoli F, De Giorgio R. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC Gastroenterol. 2014 Feb 13;14:26. doi: 10.1186/1471-230X-14-26.